Abstract
Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0–38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8–30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.
Highlights
INTRODUCTIONDespite historical pessimism about schizophrenia prognosis,[1] it has been recognised that interventions at the onset of first episode of psychosis (FEP), which is an umbrella term used to refer to schizophrenia spectrum disorders or related psychotic disorders, can improve subsequent illness outcomes.[2, 3] This recognition has led to development of early intervention services, which are founded on an assumption that duration of untreated psychosis (DUP), defined as the time from manifestation of first psychotic symptoms to initiation of adequate treatment,[4] influences treatment outcomes.[3,4,5] Despite the widespread introduction of early intervention services, individuals suffering with FEP still experience delays of approximately 1-2 years between onset of first psychotic symptoms and initiation of treatment,[6] prompting fears of serious consequences on patients’ lives, including enduring deficits and disability.[6] It is, possible that the relationship between DUP and psychosis outcomes may be a product of other factors[7, 8] related to the organisation of mental health system, treatment seeking behaviours, quality of available treatment,[9] or poor premorbid functioning
Because the length of duration of untreated psychosis (DUP) in individuals with a diagnosis of schizophrenia spectrum disorders is reported to be considerably longer compared to other psychotic disorders,[17, 30] we investigated if our findings were applicable to all individuals with first episode of psychosis (FEP) disorders or were specific to patients with first-episode schizophrenia spectrum disorders
The sample comprised 619 (86.6% of N=715) individuals of European ancestry for whom qualitycontrolled genome-wide genotyping and DUP were available. Those participants who were included in the study or excluded from the final cohort did not differ in terms of DUP, gender, marital status, employment, living arrangement and diagnoses; the former group included participants who were younger (t(1112.5)=-2.31, P=.021) and had a lower educational attainment (x2(1)=4.72, P=.030) compared to those who were included in the study (Supplementary Table 4)
Summary
Despite historical pessimism about schizophrenia prognosis,[1] it has been recognised that interventions at the onset of first episode of psychosis (FEP), which is an umbrella term used to refer to schizophrenia spectrum disorders or related psychotic disorders, can improve subsequent illness outcomes.[2, 3] This recognition has led to development of early intervention services, which are founded on an assumption that duration of untreated psychosis (DUP), defined as the time from manifestation of first psychotic symptoms to initiation of adequate treatment,[4] influences treatment outcomes.[3,4,5] Despite the widespread introduction of early intervention services, individuals suffering with FEP still experience delays of approximately 1-2 years between onset of first psychotic symptoms and initiation of treatment,[6] prompting fears of serious consequences on patients’ lives, including enduring deficits and disability.[6] It is, possible that the relationship between DUP and psychosis outcomes may be a product of other factors[7, 8] related to the organisation of mental health system, treatment seeking behaviours, quality of available treatment,[9] or poor premorbid functioning Seen in this way, DUP may be a marker of the illness severity rather than a predictor of the illness itself. We hypothesised that there will be a positive association between polygenic propensity for schizophrenia, bipolar disorder, major depression and intelligence with longer DUP in participants with a diagnosis of FEP disorders
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